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Published in final edited form as: Cancer Lett. 2025 Jan 8;612:217447. doi: 10.1016/j.canlet.2025.217447

Meeting Report: 1st International Conference on Polyploid Giant Cancer Cells—Biology, Clinical Applications, and the Birth of a New Field in Cancer Research

Tao P Wu 1,*, Xiaoran Li 3,*, Sujuan Ba 2, Phil Jones 4, Donna E Hansel 3, Jinsong Liu 3,$
PMCID: PMC12186869  NIHMSID: NIHMS2084397  PMID: 39793754

Introduction:

Over the past century, pathologists have observed the presence of distinctive large mononucleated or multinucleated giant cancer cells with multiple copies of genomes, known as polyploid giant cancer cells (PGCCs). Notably, polyploid genomes are detected in approximately 37–50% of human cancers, representing most frequently altered genetic events in cancer.

Unfortunately, the pathologists’ observations of PGCCs largely have stayed at the morphologic phenotypic level without the function of these cells, while investigators in cancer research using various model system largely ignored these big cells due to the general belief that these cells are senescent and nonviable due to their inability to undergo mitosis.

The past two decades has witnessed a transformative shift in the understanding of these cells. PGCCs represent a stress-responsive mechanism in which mitosis-independent growth mimics the early embryogenesis, impacting immortality, malignant transformation, invasion, metastasis, dormancy, and resistance.

The emerging study of PGCCs holds significant promise for understanding cancer and improving patient outcomes by enhancing therapeutic efficacy, reducing resistance, and enabling early detection. There have been significant increase in the number of investigators, PGCCs has emerged as brand-new field of cancer biology [1].

To further advance this research, the 1st International Conference on Polyploid Giant Cancer Cells (PGCCs), focusing on their biology and clinical applications, was held on February 16–17, 2024. This conference has brought together leading researchers and clinicians to explore their role in cancer biology. Fully accredited for Continuing Medical Education (CME), the conference attracted 125 registered attendees.

Conference Opening

Day 1 of the conference began with opening remarks by Dr. Donna Hansel, MD, PhD, Division Head of Pathology and Laboratory Medicine, and Dr. Giulio Draetta, MD, PhD, Senior Vice President for Research at MD Anderson Cancer Center. They warmly welcomed all speakers and attendees to this inaugural event.

The Conference Chair, Dr. Jinsong Liu, MD, PhD, introduced the conference by highlighting key milestones over the past two decades that have led to the exponential growth of research on PGCCs. He officially declared the emergence of PGCC research as a new field in cancer biology.

Dr. Donna Hansel, Conference Co-Chair, provided a historical perspective on PGCCs, provided pathological observations through various tumor slide examples featuring different types of tumor giant cells. She raised several critical unanswered questions, effectively setting the stage for a series of insightful presentations to follow.

PGCCs in Cancer Evolution

The first session, “Cancer Evolution”, Chaired by Perry Marshal and Henry Heng. This session aimed to explore the evolutionary aspects of cancer, with a specific focus on how PGCCs contribute to the complexity and diversity seen in tumor development and progression. The speakers brought forth their research findings, shedding light on the mechanisms underlying cancer evolution.

Dr. Heng featured talks on the emergence of transitional supersystems in PGCCs - Dr. Henry Heng’s talk on “PGCCs in Two-Phased Evolution: How Transitional Supersystems Emerge from Information Self-Creation” likely delved into his work on the genome theory of cancer evolution [2]. His research emphasizes the critical role of genomic instability and karyotypic alterations in driving the evolutionary trajectories of cancer. By focusing on PGCCs, Dr. Heng’s work suggests a model wherein cancer evolution can be seen as a macro-evolutionary process, involving significant genomic reorganizations that contribute to cancer’s adaptability and heterogeneity.

Dr. Nick Navin talked on chromosome evolution in breast cancer. He presented on “Punctuated Chromosome Evolution in Breast Cancer and Beyond,” a topic that aligns with his pioneering contributions to the field of single-cell genomics in cancer. Dr. Navin’s research has been instrumental in uncovering the clonal evolution of tumors, demonstrating how large-scale chromosomal changes can occur in a punctuated, rather than gradual, manner [3]. This talk explored how these dramatic genomic events contribute to cancer diversity and the role of PGCCs in facilitating these processes.

Dr. Jekaterina Erenpreisa discussed on “Cancer Attractors in Evolution of Human Genome” would have presented her research on the phenomenon of cancer cell reprogramming and the emergence of attractor states within the evolutionary landscape of tumors [4]. She reports multiple layers of evolutionary attractors in cancer development and provides a compelling framework for understanding cancer’s ability to evolve and adapt through mechanisms reminiscent of embryonic development stages.

Dr. Amy Bowes and Dr. Funan He presented on the genomic landscape of PGCCs in sarcomas and the role of genomic instability in cancer evolution, respectively. Dr. Bowes’ research focused on how PGCCs represent a form of evolutionary dead-end or a potential source of new genetic diversity within tumors. Dr. He’s work on genomic instability could have explored how these chaotic genomic changes drive the evolutionary processes within tumors, a distinct genomic and transcriptomic landscape of WGD tumors and potential driver genes in this process.

Models for PGCCs

Following a lunch and poster session, the conference transitioned into second session “Models for PGCCs,” Chaired by Dr. Subrata Sen. The aim of this session was to explore various models that help elucidate the role of PGCCs in cancer through different lenses, from Drosophila models to mouse glioblastoma studies, offering a spectrum of perspectives on how unscheduled polyploidy influences cancer dynamics.

Dr. Wu-Min Deng presented on “Polyploidy in Drosophila Tumor Models,” likely drawing on his expertise in developmental biology and genetics to demonstrate how Drosophila, as a model organism, can be used to study the mechanisms and consequences of polyploidy in tumor growth [5]. His group found that tumorigenesis-prone polyploid transitional zone cells play a critical role as leading cells in tissue extension during adult salivary gland morphogenesis. His research has contributed to understanding the cellular and molecular bases of tumor development, using Drosophila as model system.

Dr. Brian Calvi’s talk on “Using Model Organisms to Define the Effects of Unscheduled Polyploidy on Tissue and Tumor Growth” highlighted his research on cell cycle regulation, chromosome duplication, and genome stability. Using model organisms like fruit flies, Dr. Calvi’s work provides insights into how polyploidy affects cellular functions, with potential implications for understanding tumor growth and the development of cancer therapies [6].

Dr. Jian Hu focused on “Defective Lipid Metabolism Drives Genomic Instability in Glioblastoma,” a presentation that could have explored his findings on the metabolic alterations in cancer cells in glioblastoma, and how these changes contribute to genomic instability and cancer progression. The histologic images of PGCCs in his glioblastoma mouse model has impressed all attendees deeply. Dr. Hu’s research offers a link between metabolic pathways and the genetic changes driving cancer, providing a basis for potential therapeutic interventions targeting metabolism in PGCCs in glioma.

The Role of PGCCs Cell in Transformation

Then, the Session 3, “Cell Transformation and the Role of PGCCs”, chaired by Drs. Dihua Yu and Tao Wu. The session highlighted the complex roles of PGCCs in cancer biology, from their interactions with infectious agents to their involvement in the transformation processes of leukemia and their unique mechanisms of division.

Dr. Georges Herbein’s presentation on “Exploring PGCCs Emerging Role in Cytomegalovirus Infection” likely drew on his expertise in virology and infectious diseases, particularly his work on the cytomegalovirus (CMV) and its interactions with host cells. Given his research on how CMV infection can lead to cellular changes and contribute to cancer development, Dr. Herbein’s talk explored the link between viral infection, PGCC formation, and cancer progression, highlighting the role of viruses in modulating cancer cell biology [7].

Dr. Stavroula Kousteni discussed “PGCCs in Leukemia Transformation”, Her work has focused on the bone marrow microenvironment, signaling pathways in bone biology, and their impact on cancer development. Her presentation could have illuminated how PGCCs contribute to the transformation processes in leukemia, potentially offering new insights into the pathogenesis of leukemia and identifying novel therapeutic targets.

Dr. Xiaoran Li’s talk on “Novel Nuclear and Cell Division of PGCCs” and his contributions to understanding the unique mechanisms of cell division in PGCCs. His work involves exploring the unconventional pathways through which PGCCs undergo nuclear and cell and their role in tumor heterogeneity and therapy resistance [8].

Holistic View of Embryogenesis, Tumorigenesis and Resistance

The day concluded with a chair’s lecture given by Dr. Jinsong Liu from MD Anderson Cancer Center, moderated by Donna Hansel and Dean Tang. As a pathologist physician scientist, Liu’ s lecture aimed to synthesize the diverse disciplines from the basic biology of PGCCs to their clinical implications, and to propose a unified framework for understanding their role in cancer.

Dr. Liu draw fascinating parallels between the cellular mechanisms in embryogenesis and the formation of PGCCs. His research on the reprogramming of cancer cells into a blastomere-like pluripotent stem cell-like state suggests that PGCCs exploit similar mechanisms to those used during early embryonic development for dedifferentiation and promote tumor growth and survival [911].

Based on these experimental data and 30 years’ direct pathologic observation as a diagnostic pathologist, Dr. Liu proposed a “life code” theory demonstrates how PGCCs contribute to tumor heterogeneity and the dynamic evolution of cancer, resembling early stage of embryogenesis [1214]. Addressing the challenge of therapeutic resistance, Dr. Liu provided evidence that PGCCs can evade chemotherapy and offer a novel target cells for therapies. [1516].

By integrating the embryogenesis, tumorigenesis, and therapeutic resistance through the life cycle of PGCCs, Liu’s lecture provides a simple framework to explain the tumor heterogeneity or complexity, offer new direction for diagnosis, treatment, and ultimately, patient care improvement.

The session is followed by group photo session and welcome dinner, Fig. 1Fig.4, and sFig.1. The meeting program is shown in sTable 1 and abstracts in sTable 2.

Figure 1:

Figure 1:

Jinsong Liu, Conference Chair (left) and Donna Hansel (Conference Co-Chair, right).

Figure 4.

Figure 4.

Meeting scenes: upper, back view; Low, front view

The Emergence of Resistance

The Day 2 of the conference started from the Session 4. The Emergence of Resistance, chaired by Drs. Anil Sood and James You. This session aimed to shed light on the complexities of cancer resistance mechanisms, exploring physical as well as the roles of polyploidy and cellular senescence in the context of evolving tumor microenvironments.

Dr. Michelle Dawson’s presentation on “Physical and Metabolic Aspects of Therapy Induced Senescence and Polyploidy” likely drew from her expertise in the biomechanical properties of cancer cells and how these properties contribute to drug resistance and cancer progression. Her work has emphasized the importance of the physical microenvironment and cellular mechanics, providing a unique lens through which to examine therapy-induced changes in cancer cells [17].

Dr. Kenneth Pienta tackled “The Emergence of Cancer Resistance” by likely building upon his extensive research into the cancer evolution and tumor microenvironment, specifically focusing on how cancer cells evolve to resist therapies. His studies on the dynamics of cancer cell communities offer insights into overcoming resistance [18].

Dr. James Jackson’s focus on “The Phagocytic Phenotype of Tumor Cells Made Senescent by Chemotherapy” would have introduced groundbreaking concepts based on his research into how chemotherapy-induced senescence affects cancer cell behavior, particularly the acquisition of phagocytic properties that may contribute to therapy resistance and tumor progression [19].

Dr. Tao Wu presented on “Retrotransposable Elements Mediate the Drug-Tolerant Persistence in Chemo-Treatment,” which could draw from his research interests in genetic and epigenetic mechanisms of cancer development. This talk explored how retrotransposable elements contribute to cancer cell survival and resistance in the face of chemotherapy, offering a genetic perspective on the challenge of drug resistance.

Dr. Bruno Sainz Jr.’s discussion on “Genotoxic Resistance in Pancreatic Ductal Adenocarcinoma is Driven by a Programmed Process Combining Polyploidism, Senescence, and Stemness” would have highlighted his research into the molecular mechanisms driving pancreatic cancer progression and resistance. By focusing on the interplay between polyploidies, cellular senescence, and cancer stemness, Dr. Sainz offered insights into potential vulnerabilities in pancreatic cancer that could be targeted therapeutically.

Novel Targets and Agents for Therapy

The Session 5: Novel Targets for Therapy, chaired by Drs. Rugang Zhang and Azra Raza centered on identifying and discussing new therapeutic targets within the realm of PGCCs. The session featured detailed discussions on various strategies to target PGCCs in cancer therapy, from hematologic malignancies to lung and breast cancers.

Dr. Azra Raza discussed “Polyploid Giant Cancer Cells in Hematologic Malignancies as Potential Therapeutic Targets,” leveraging her extensive research on myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Her work, which focuses on the pathogenesis of MDS and AML and the search for effective treatments, would have provided a strong basis for discussing the potential of targeting PGCCs in blood cancers. Dr. Raza’s presentation explored how PGCCs contribute to treatment resistance seen in hematologic malignancies and on how targeting these cells as a new therapeutic avenue [20].

Dr. Christina Voelkel-Johnson and Dr. Mike Xu presented on strategies to interfere with stress- induced polyploidization and the nuclear envelope alterations in carcinogenesis and chemo- resistance, respectively. Dr. Voelkel-Johnson, known for her work on prostate cancer and the role of sphingolipid metabolism in cancer biology, discussed how stress conditions in the tumor microenvironment led to polyploidization and how this can be targeted. Dr. Xu, with his expertise in nuclear dynamics in cancer, likely focused on the structural and functional changes in the nuclear envelope of PGCCs as a novel target for therapy. [2122]

Dr. Vural Tagal and Dr. Yu-Chih Chen explored targeting PGCCs in lung and breast cancers, presenting innovative approaches to therapy. Dr. Tagal’s research on characterizing and modeling PGCCs in these cancers could have detailed the unique features of PGCCs that make them viable targets for therapy [23]. Dr. Chen’s work on discovering inhibitors of PGCCs through single-cell analysis might have highlighted new methodologies in identifying and targeting the vulnerabilities of PGCCs [24].

Polyploid-Macrophage Fusion in Early Detection, Metastasis, and Prognosis

After lunch, the Session 6: Polyploid-Macrophage Fusion in Early Detection, Metastasis, and Prognosis, Chaired by Drs. Robert C. Bast and Donna Hansel, emphasized the significance of the interaction between polyploid giant cancer cells (PGCCs) and macrophages, a topic critical for understanding cancer’s ability to metastasize, evade detection, and impact patient prognosis.

Dr. Melissa Wong discussed “Macrophage-Tumor Cell Fusion: Impact on Tumor Progression, Early Detection, and Measure of Treatment Response,” drawing on her expertise in cell biology and cancer research. Her work has often explored the cellular mechanisms by which cancer spreads and how the tumor microenvironment influences cancer progression. This presentation highlighted the role of cell fusion events between macrophages and PGCCs in facilitating tumor heterogeneity and metastasis and monitoring of treatment efficacy [25].

Dr. Steven Lin presented on “Blood PGCCs in Lung Cancer Prognosis and Clinical Outcome,” a topic that fits well with his research interests in radiation oncology and the molecular mechanisms underlying cancer therapy response. Dr. Lin’s focus on PGCCs in the bloodstream likely explored how these cells can be used as biomarkers for prognosticating lung cancer outcomes, understanding the metastatic process, and evaluating patient responses to therapy [26].

Daniel J. Gironda from Dr. Daniel Adam’s group discussed “Hypertrophy of Polyploid Cancer Associated Macrophage-Like Cells in Circulation Correlates with Multi-Organ Metastatic Spread in Human Solid Tumors’, an intriguing presentation that explored their research into the systemic effects of cancer on the body, particularly how PGCCs and macrophage-like cells in the bloodstream relate to the spread of cancer to multiple organs [27].

Future Directions of PGCCs

The Open Discussion and Future of PGCCs session was chaired by Dr. Phil Jones and Sujuan Ba and one representative speakers from each session. The moderators and panelists, Bryan Calvi, Henry Heng, George Herbein, Azra Raza, Michelle Dawson, Mellisa Wong, and Jinsong Liu, discussed interactive segment of the conference designed to foster dialogue among participants about the current state, challenges, and future directions of PGCC research.

  • Conceptual Revolution in Cancer Research: The discussion had explored how PGCC research can lead to a deeper understanding of cancer’s complexity, potentially reshaping diagnostic, prognostic, and therapeutic strategies.

  • Platform to Identify Anti-PGCC Drugs: A significant portion of the dialogue likely focused on the translation of basic PGCC research into clinical applications, particularly the identification and development of novel anti-PGCC agents.

  • Clinical Trials with Anti-PGCC Agents: The conversation had delved into the practical aspects of bringing PGCC-targeted therapies from the bench to the bedside, including the design of clinical trials, patient selection criteria, and biomarkers for assessing treatment efficacy and safety.

  • Early Detection and Prognosis: Given the potential role of PGCCs in tumor progression and metastasis, the discussion had highlighted the importance of developing PGCC-based biomarkers for early cancer detection and prognosis..

  • Collaboration and Multidisciplinary Approaches: Recognizing the deep biology behind the complexity of PGCCs, participants were encouraged to consider the benefits of interdisciplinary collaborations, bringing together experts from genomics, bioinformatics, pathology, oncology, and pharmacology to accelerate progress in understanding and targeting PGCCs.

The Q and A sessions were intensive from speakers during entire meeting. Small groups discussions were intensive and carried out during breaks and in the evening of February 16 dinner and after the dinner. In addition, there were intensive discussion during poster sessions. Several posters highlights the mechanisms of potential differentiation therapies and prognostic significance following chemotherapy. Further, it was noted that multiple terminology was used to describe same the phenomenology, attendees are encouraged to use the most used and accepted terminology “Polyploid Giant Cancer Cells” for the future communication.

At the end, Jinsong and Donna summarized all the sessions and wrapped up the 1st International Conference on PGCCs with a “Closing Remarks” on 4:00 pm of February 17.

Supplementary Material

Supplemental Figure 1: Additional Conference Portraits

sFigure 1. Additional Images of Conference Attendees

Supplemental Table 1- Final Program

sTable 1. The meeting program.

Supplemental Table 2- Meeting Abstracts

sTable 2. The meeting abstracts.

Figure 2.

Figure 2.

Speakers and Session Chairs. Top row: Xiaoran Li, Yu-Chi Chen, Dean Tang, Bruno Sainz, Michelle Dowson, Amy Bower, Stavroula Kousteni, Tao Wu, Perry Marshall; Middle Row, Mike Xu, Subrata Sen, Georges Herbein, James You, Henry Heng, Dihua Yu, Hunan He, Christine Voekel-Johnson, Melissa Wong, James Jackson. Front row: Ken Pienta, Katrina Erenpreisa, Jinsong Liu, Azra Raza, Sujuan Ba, Jian Hu, Bryan Calvi, Wu-Min Deng, Daniel Gironda

Figure 3.

Figure 3.

Group Photo of conference attendees

Highlights:

  1. A comprehensive overview of the inaugural international conference on polyploid giant cancer cells (PGCCs) that we held in February 16–17.

  2. Experts from diverse disciplines to discuss the biological significance and clinical implications of PGCCs.

  3. Establishment of a new field in cancer research, their role in therapy resistance and metastasis, and emerging clinical applications targeting these unique cancer cell populations.

  4. Summarization of key presentations, discussions, and breakthroughs shared during the conference and is accompanied by a curated collection of abstracts submitted by leading researchers in the field.

References:

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplemental Figure 1: Additional Conference Portraits

sFigure 1. Additional Images of Conference Attendees

Supplemental Table 1- Final Program

sTable 1. The meeting program.

Supplemental Table 2- Meeting Abstracts

sTable 2. The meeting abstracts.

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